Abstract
Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.
Highlights
New effective drugs are needed to prevent the potentially deadly complications of COVID-19 (Woolf et al, 2020; Faust et al, 2021; Woolf et al, 2021) and thereby reduce its fatality rate (Uckun, 2020a; Uckun, 2020b; Uckun et al, 2020a; Zheng et al, 2020; Zhou et al, 2020)
The pharmacokinetics of Artemisinin after a single oral dose was examined in multiple small clinical studies employing Artemisinin most often at the clinically active 500 mg dose level alone or in combination with other antimalarial drugs, such as piperaquine, and showed a rapid elimination within 2–3 h (Duc et al, 1994; De Vries et al, 1997; Ashton et al, 1998; Gordi et al, 2002; Hien et al, 2011; Wang et al, 2020; Li et al, 2021)
The reported anti-inflammatory and immunomodulatory effects of Artemisinin and its derivatives have been attributed to their ability to inhibit the pro-inflammatory nuclear factor kappa B (NF-κB) signaling pathway leading to reduced TNF-α and IL-6 levels as well as the Smad2/3-dependent TGF-β signaling pathway (Aldieri et al, 2003; Xu et al, 2007; Wu et al, 2010; He et al, 2011; Mo et al, 2012; Li et al, 2013; Jiang et al, 2016; Zhang et al, 2020)
Summary
New effective drugs are needed to prevent the potentially deadly complications of COVID-19 (Woolf et al, 2020; Faust et al, 2021; Woolf et al, 2021) and thereby reduce its fatality rate (Uckun, 2020a; Uckun, 2020b; Uckun et al, 2020a; Zheng et al, 2020; Zhou et al, 2020) The goal of this mini-review is to discuss the emerging evidence regarding the clinical potential of Artemisinin for the treatment of COVID-19. There are several Phase II/III studies currently underway in which pharmaceutical compositions or supplements containing Artemisinin and/or its derivatives are being evaluated as adjuncts to the standard of care in COVID-19 patients, including but not limited to Artesunate plus Artemisinin (NCT04387240), Artesunate plus amodiaquine (NCT04502342); Artesunate plus pyronaridine (NCT04475107), Artusunate as well as Artemisia annua (NCT04374019). Adaptive clinical trials will be required for the identification of the most promising treatment regimens (Uckun, 2020b)
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